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1.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338033

ABSTRACT

Neutrophils are vital in defence against pathogens but excessive neutrophil activity can lead to tissue damage and promote acute respiratory distress syndrome (ARDS). COVID-19 is associated with systemic expansion of immature neutrophils but the functional consequences of this shift to immaturity are not understood. We used flow cytometry to investigate activity and phenotypic diversity of circulating neutrophils in acute and convalescent COVID-19 patients. First, we demonstrate hyperactivation of immature CD10- subpopulations in severe disease, with elevated markers of secondary granule release. Partially activated immature neutrophils were detectable three months post symptom onset, indication long term myeloid dysregulation in convalescent COVID-19 patients. Second, we demonstrate that neutrophils from moderately ill patients downregulate the chemokine receptor CXCR2, while neutrophils from severely ill individuals failed to do so, suggesting altered ability for organ trafficking and a potential mechanism for induction of disease tolerance. CD10- and CXCR2hi neutrophil subpopulations were enriched in severe disease and may represent prognostic biomarkers for identification of individuals at high risk of progressing to severe COVID-19.

2.
Am J Epidemiol ; 191(7): 1153-1173, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1740791

ABSTRACT

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Cohort Studies , Humans , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , United States/epidemiology , Young Adult
3.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277558

ABSTRACT

Rationale The pulmonary vasculature is critical for gas exchange, impacts both pulmonary and cardiac function, and has renewed importance due to COVID-19. Pulmonary blood volume is, however, technically difficult to assess, generally requiring invasive methodology for quantification. Prior studies are limited in size and participant enrollment was selective;therefore, variation in the general population is largely unknown. We performed contrast-enhanced dual-energy computed tomography (DECT) in a multicenter, community-based cohort to describe variation in pulmonary perfused blood volume (PBV) in the community. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) recruited adults from six sites. The MESA Lung Study invited all MESA participants attending Exam 6 (2017-18), excluding those with kidney disease and contrast allergy, to undergo DECT at functional residual capacity via Siemens Flash or Force scanner: CareDose on, pitch 0.55, 0.25 sec exposure, 0.5mm slice thickness, iterative reconstruction (Admire) with Qr40 Kernel. Half concentration 370mg/ml Iopamidol was delivered at 4ml/s for the full scan, starting 17 seconds prior to scanning, including a ∼4 sec breath hold. PBV was calculated by material decomposition and normalized with iodine concentration in the pulmonary trunk. Generalized linear regression models included age, sex, race/ethnicity, height, weight, smoking status, site, and education.ResultsDECT scans were acquired for 714 participants, 36 of which were excluded due to image quality. Mean age of the remaining 678 participants was 71 years (range 63 - 79), 55% were male, 51% were ever smokers, and the race/ethnic distribution was 41% White, 29% Black, 17% Hispanic, and 13% Asian. Mean PBV was 468 + 151mL. The strongest demographic correlate was lower PBV with greater age (-30 mL per 10 years, 95% CI: -43, -18, p<0.001). Pulmonary PBV was positively associated with height, weight, and male sex (all P<0.001). PBV was lower in former compared to never smokers (p =0.04) and in Black than White participants (p=0.002), but not in Hispanic or Asian participants. There were no consistent differences across education or study site. Results were similar after adjustment for lung function and percent emphysema on CT.ConclusionsTo our knowledge, this is the first assessment of pulmonary PBV in a large, multiethnic, general community sample. Pulmonary PBV assessed by contrast-enhanced DECT was substantially reduced with advancing age and varied with body size, sex, former smoking, and, to a lesser extent, Black race. Understanding variation in pulmonary PBV in the general population may elucidate risk of cardiopulmonary disease and physical function.

4.
Genome Med ; 13(1): 66, 2021 04 21.
Article in English | MEDLINE | ID: covidwho-1197350

ABSTRACT

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. RESULTS: We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. CONCLUSIONS: These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.


Subject(s)
Bronchi , COVID-19/genetics , Respiratory Mucosa , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Asthma/genetics , COVID-19/immunology , Cardiovascular Diseases/genetics , Cardiovascular Diseases/immunology , Gene Expression , Genetic Variation , Humans , Middle Aged , Obesity/genetics , Obesity/immunology , Pulmonary Disease, Chronic Obstructive/genetics , Quantitative Trait Loci , Risk Factors , Smoking/genetics
5.
Ann Intern Med ; 173(10): 782-790, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-690212

ABSTRACT

BACKGROUND: Obesity is a risk factor for pneumonia and acute respiratory distress syndrome. OBJECTIVE: To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: A quaternary academic medical center and community hospital in New York City. PARTICIPANTS: 2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation. MEASUREMENTS: Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis. RESULTS: Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). This association was primarily observed among patients younger than 65 years and not in older patients (P for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis. LIMITATIONS: Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias. CONCLUSION: Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older. PRIMARY FUNDING SOURCE: National Institutes of Health.


Subject(s)
Betacoronavirus , Body Mass Index , Coronavirus Infections/epidemiology , Intubation, Intratracheal/statistics & numerical data , Obesity/epidemiology , Pneumonia, Viral/epidemiology , Academic Medical Centers , Age Factors , Aged , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19 , Cohort Studies , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Hospitals, Community , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , New York City/epidemiology , Pandemics , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Troponin/blood
6.
BMJ ; 369: m1996, 2020 05 29.
Article in English | MEDLINE | ID: covidwho-423282

ABSTRACT

OBJECTIVE: To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. DESIGN: Retrospective manual medical record review. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. PARTICIPANTS: The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. MAIN OUTCOME MEASURES: Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. RESULTS: Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. CONCLUSIONS: Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.


Subject(s)
Coronavirus Infections/epidemiology , Hospitalization/statistics & numerical data , Pneumonia, Viral/epidemiology , Academic Medical Centers/statistics & numerical data , Acute Kidney Injury/virology , Adolescent , Adult , Aged , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Cough/virology , Dyspnea/virology , Emergency Service, Hospital/statistics & numerical data , Female , Fever/virology , Humans , Intensive Care Units/statistics & numerical data , Intubation , Length of Stay , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Young Adult
7.
N Engl J Med ; 382(25): 2411-2418, 2020 06 18.
Article in English | MEDLINE | ID: covidwho-217993

ABSTRACT

BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).


Subject(s)
Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Intubation/statistics & numerical data , Pneumonia, Viral/drug therapy , Treatment Failure , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , Hospitalization , Humans , Male , Middle Aged , New York City , Pandemics , Pneumonia, Viral/mortality , Propensity Score , SARS-CoV-2
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